Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

Abstract

Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos oxon, and iso-OMPA demonstrates that other important targets exist. The goal of this work is to identify non-acetylcholinesterase targets of organophosphorus toxicants. Three living mice were treated with a dose of biotinylated organophosphate that was not toxic to the mice. The biotinylated proteins were extracted by binding to avidin-sepharose, and separated by gel electrophoresis. Coomassie stained bands were digested with trypsin, and identified by their fragmentation patterns on a quadrupole time of flight mass spectrometer. It was found that albumin was labeled by the biotinylated organophosphate. Tissues from untreated mice showed no albumin by mass spectroscopy. Confirmation that albumin was labeled by the organophosphate was obtained by Western blotting where the biotinylated organophosphate was visualized with Streptavidin Alexa 680. Mouse, bovine, and human albumin reacted with biotinylated organophosphate. It is concluded that albumin is a new biomarker of organophosphorus agent exposure.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2004
Accession Number
ADA427269

Entities

People

  • Oksana Lockridge

Organizations

  • University of Nebraska Medical Center

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Biological Markers
  • Blood
  • Blood Proteins
  • Chemical Analysis
  • Chemical Kinetics
  • Chemistry
  • Enzyme Inhibitors
  • Gel Electrophoresis
  • Insecticides
  • Mass Spectrometers
  • Mass Spectrometry
  • Mass Spectroscopy
  • Organophosphates
  • Pesticides
  • Spectrometry
  • Spectroscopy

Readers

  • Molecular and Cellular Biochemistry
  • Neurotoxicology